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Endocrine Therapy of Breast Cancer

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Breast cancer remains one of the first leading causes of death in women, and currently endocrine treatment is of major therapeutic value in patients with estrogen-receptor positive tumors. Selective estrogen-receptor modulators (SERMs), such as tamoxifen and raloxifene, aromatase inhibitors, and GnRH agonists are the drugs of choice. Tamoxifen, a partial nonsteroidal estrogen agonist, is a type II competitive inhibitor of estradiol at its receptor, and the prototype of SERMs. Aromatase inhibitors significantly lower serum estradiol concentration in postmenopausal patients, having no detectable effects on adrenocortical steroids formation, while GnRH agonists suppress ovarian function, inducing a menopause- like condition in premenopausal women. Endocrine therapy has generally a relatively low morbidity, leading to a significant reduction of mortality for breast cancer. The aim of chemoprevention is to interfere early with the process of carcinogenesis, reducing the risk of cancer development. As preventive agents, raloxifene and tamoxifene are equivalent, while raloxifene has more potent antiresorptive effects in postmenopausal osteoporosis. Endocrine treatment is usually considered a standard choice for patients with estrogen-receptor positive cancers and non-life-threatening advanced disease, or for older patients unfit for aggressive chemotherapy regimens. Several therapeutic protocols used in patients with breast cancer are associated with bone loss, which may lead to an increased risk of fracture. Bisphosphonates are the drugs of choice to treat such a drug-induced bone disease. The aim of this review is to outline current understanding on endocrine therapy of breast cancer.

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Keywords: Bisphosphonates; Breast cancer; Early Breast Cancer Trial-ists' Collaborative Group (EBCTCG); GnRH agonists; Non-steroidal anti-inflammatory drugs (NSAIDs); Osteonecrosis; SERM; Selective estrogen-receptor modulators; adjuvant therapy; adrenalec-tomy; aromatase inhibitors; atypical hyperplasia; carcinogenesis; chemoprevention; clodronate; cyclooxygenase (COX); dual-energy x-ray absorptiometry (DXA); endocrine therapy; estradiol; estrogen-receptor positive tumors; gonadotropin-releasing hormone (GnRH); hypophysectomy; ibandronate; lymph node; ovarian suppres-sive drugs; ovariectomy; postmenopausal osteoporosis; progesterone-receptor; prophylaxis; raloxifene; risedronate; serum estradiol; tamoxifen

Document Type: Research Article

Publication date: 2011-02-01

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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